The long-term objective of this research project is the investigation of the lipid-lipid interactions in phospholipid bilayers. Specifically, we aim to (1) investigate the gel liquid less than and greater than liquid crystalline phase transition of a wide range of saturated liked-chain phosphatidylcholines (PCs) in aqueous dispersions. The study will utilize highly purified (typically 99 mol %) PCS and involve the thermodynamic (delta S and delta V) and structural (gauche/trans ratio, bilayer or micelle organization) measurements; (2) study the possible coupling between the outer and the inner monolayer of the mixed-chain PC bilayers. The mixed-chain PCs to be employed for this investigation are highly asymmetrical, namely, the number of carbon atoms in sn-2 chain is smaller than that in sn-1 by four or more such as C(18):C(14)-PC and C(18):C(12)-PC; (3) investigate saturated PC vesicle-vesicle aggregation/fusion at tempeature below the phase transition temperature (Tm); (4) continue our investigation of the role of cholesterol in bilayers; particularly, the interaction of cholesterol with lyso PC and various gangliosides. Principal techniques to be used are high-sensitivity differential scanning calorimetry, differential densimetry, analytical ultracentrifuge, NMR and Raman spectroscopy. Information gained from this proposal will add new dimension of our current knowledge about lipid-lipid interaction in biological membranes.